Predictors of cognitive decline and treatment response in a clinical trial on suspected prodromal Alzheimer's disease

Stefan J Teipel (1) , Enrica Cavedo (2) , Michel J Grothe (3) , Simone Lista (4, 5) , Samantha Galluzzi (4) , Olivier Colliot (6, 4, 7) , Marie Chupin (6) , Hovagim Bakardjian (4) , Didier Dormont (6, 7) , Bruno Dubois (5, 4) , Harald Hampel (4) , Olivier Godefroy (8, 9)

1 University of Rostock
2 UPMC - Université Pierre et Marie Curie - Paris 6
3 DZNE - German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen
4 IM2A - Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre]
5 ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute
6 ARAMIS - Algorithms, models and methods for images and signals of the human brain = Algorithmes, modèles et méthodes pour les images et les signaux du cerveau humain [ICM Paris]
7 CHU Pitié-Salpêtrière [AP-HP]
8 CHU Amiens-Picardie
9 LNFP - Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559

We determined the value of hippocampus (Hp) and basal forebrain (BF) volumes for predicting cognitive decline and treatment response in a double-blind, randomized, placebo-controlled phase 4 trial at 28 academic centers (France) in patients with amnestic mild cognitive impairment (MCI) receiving Donepezil 10 mg daily or placebo over 12 months, and 6 months open label follow-up. Outcome measures were the rates of global and domain specific cognitive decline as non-primary efficacy endpoint. The intention-to-treat (ITT) sample analyzed comprised 215 cases. Baseline Hp volume was a significant predictor of rates of change in global cognitive function in linear mixed effects models. This effect was independent of treatment. BF volume was not associated with rates of global or domain specific cognitive decline. Rates of delayed free recall decline were higher in MCI cases treated with donepezil compared to placebo. Only Hp, but not BF volume was a useful predictor of cognitive decline in suspected prodromal AD patients. Both Hp and BF volumes were poor predictors of treatment response, questioning previous approaches on predicting treatment response without placebo control. clinicalTrials.gov Identifier NCT00403520.

Domaines: Traitement du signal et de l'image [eess.SP]; Vision par ordinateur et reconnaissance de formes [cs.CV]; Imagerie médicale; Traitement des images [eess.IV]; Imagerie; Neurobiologie

Stefan J Teipel, Enrica Cavedo, Michel J Grothe, Simone Lista, Samantha Galluzzi, et al.. Predictors of cognitive decline and treatment response in a clinical trial on suspected prodromal Alzheimer's disease. Neuropharmacology, 2016, 108, pp.128-35. ⟨10.1016/j.neuropharm.2016.02.005⟩. ⟨hal-01372417⟩